高原低氧免疫损伤及其干预措施的研究

Study of hypoxia-induced immune injury and its intervention measure

目的:探讨高原低氧损伤免疫系统的特征及其可能机制,研究高原低氧免疫损伤的干预措施。方法:测定低氧暴露不同时间小鼠免疫器官指数、外周血和免疫器官T淋巴细胞亚群的变化;观察小鼠免疫器官淋巴细胞凋亡率及小鼠肺脏和肾脏病理学改变。采用预防给药方式,研究中药组方对低氧免疫损伤小鼠的干预作用。结果:①模拟海拔8000m低氧暴露8h后,小鼠胸腺CD4+CD8+细胞数显著下降,CD4+CD8-、CD4-CD8+细胞数显著增加(P<0.01);低氧暴露3d后,外周血CD4+细胞明显减少(P<0.05),CD4+/CD8+比值显著降低(P<0.05),胸腺CD4+CD8+细胞数进一步下降,CD4+CD8-、CD4-CD8+细胞数进一步增加,小鼠脾脏、胸腺淋巴细胞晚期凋亡和坏死率均显著增加(P<0.05);低氧暴露6d后,小鼠脾指数显著性增加(P<0.01);胸腺指数显著性降低(P<0.01),脾CD4+、CD8+细胞数显著降低(P<0.01),脾脏和胸腺淋巴细胞晚期凋亡率和坏死率进一步增加(P<0.01),活细胞率显著降低(P<0.01),脾脏淋巴细胞早期凋亡率显著增加(P<0.01)。整个低氧暴露过程中外周血CD8+无显著性变化。②新复方党参、香杞多糖、二者联合应用均能显著增加低氧免疫损伤小鼠外周血CD3+、CD4+、脾脏CD4+的细胞水平(P<0.01,P<0.05),对脾脏CD8+细胞水平没有显著影响。香杞多糖及其与新复方党参联合应用均能进一步降低胸腺CD4+CD8+,进一步增加CD4+CD8-的细胞水平(P<0.01),未见对CD4-CD8+细胞水平的影响;新复方党参对低氧免疫损伤小鼠胸腺没有显著性影响。结论:模拟海拔8000m低氧暴露后小鼠外周发挥免疫作用的淋巴细胞数减少可能与低氧暴露早期淋巴细胞凋亡率和坏死率增加和肺脏淋巴细胞分布增多有关。新复方党参和香杞多糖作为低氧免疫损伤干预措施,具有一定发展前景。

Objective：To explore the characteristic of hypoxia-induced immune injury,its mechanisms and the intervention measure. Methods： The change of immune organ index,T lymphocyte subsets of peripheral blood and immune organ in mice during hypoxia were detected. Lymphocyte apoptosis of immune organ,pathology of lung and kidney in mice were observed. Then by way of prophylaxis we studied the effect of Chinese Traditional Medicine on hypoxia-induced immune injury in mice. Results： ① Exposure to hypoxia at 8 000 m simulated altitude for 8 h resulted in marked decrease in CD4＋CD8＋ thymocytes and marked increase in CD4＋CD8-,CD4-CD8＋ thymocytes （P0.01）. After 3 days of hypoxia,the mice had a much lower percentage of CD4＋ T-cell （P0.05）. The ratio of CD4＋/CD8＋ decreased significantly and aforesaid changes of thymocyte were further enlarged. Also mice had a pronounced increase in rates of late apoptosis or necrosis of spleen lymphocyte and thymocyte （P0.05）. After 6 days of hypoxia,index of spleen was significantly increased （P0.05）,index of thymus was significantly decreased （P0.05） and CD3＋,CD4＋,CD8＋ lymphocyte percentage of spleen were significantly decreased （P0.01）. Also late apoptosis or necrosis lymphocytes of spleen and thymus were further increased （P0.01）,viable cell rates of spleen lymphocyte and thymocytes were markedly decreased （P0.01）,early apoptosis rates of spleen lymphocyte were markedly increased （P0.01）. There was no significant change in the percentage of CD8＋ lymphocyte in peripheral blood during the whole hypoxia period. ② New Compound Codonopsis Pilosula（NCCP）,Xiang Qi Polysaccharide（XQP）and NCCP＋XQP could significantly increase the number of peripheral blood CD3＋、CD4＋ and spleen CD4＋,but had no significant influence on the number of spleen CD8＋. XQP and XQP＋NCCP could significantly decrease the number of CD4＋CD8＋ （P0.01）,increase that of CD4＋CD8-（P0.01）,and had no significant influence on CD4-CD8＋ in thymus. However,NCCP didn’t influence the component of thymocytes. Conclusion： After hypoxia at 8 000 m simulated altitude decrease of lymphocyte of periphery in mice may be related with increase of apoptosis and necrosis of lymphocyte,and with increase of distribution of lymphocyte to lung in early period of exposure. NCCP and XQP have hopeful prospect in intervention study of hypoxia-induced immune injury.